The research projects proposed in this application are concerned with two problems, both of which deal with cholinergic synaptic transmission. The first project uses alpha-bungarotoxin, alpha-mambatoxin and additional toxins which block activation of nicotinic acetylcholine receptors on nerve cells to determine the relationship between the receptor and the molecule which binds alpha-bungaratoxin. This project will be conducted first using clonal cell lines and later central nervous system tissue to study structure, metabolism and regulation of acetylcholine receptors on nerve. The second project uses a murine model of myasthenia gravis to address specific questions about the production of paralysis. Immunological, genetic, and morphological experiments will use our documented strain dependence of paralysis as a means of examining separately the various mechanisms which might cause paralysis. Neuromuscular junctions from high and low responder strains will be studied in vitro to determine effects of antibodies on receptor degradation.